The overall focus of this PPG is on autonomic and vascular mechanisms engaged by low skeletal muscle oxygen tension, and their role in disease. The goal of Project 4 is to examine the effects of acute and intermittent hypoxic stress, two fundamental and prevalent types of physiologic stress, on circulatory control. Hypoxia is common in smokers, and intermittent hypoxia is characteristic of obstructive sleep apnea. Regional skeletal muscle hypoxia (ischemia) is also present during exercise and is pronounced in peripheral arterial disease. All of these conditions are marked by increased cardiovascular risk. It is well established that hypoxia and ischemia exert their effects on the circulation via integrated and at times competing influences on the autonomic nervous system and local metabolic control. Preliminary data from our laboratory demonstrate that in healthy humans intermittent hypoxia leads to sustained sympathetic activation. Because the antioxidant ascorbic acid attenuates the sympathoexcitatory effect of intermittent hypoxia, oxidative stress may be involved. We also found that sympathetic reflex responses to hypoxia are enhanced in patients with sleep apnea and are normalized in part by continuous positive airway pressure therapy. Similarly, in preliminary studies, ascorbic acid appears to attenuate the chemoreflex sensitizing effect of intermittent hypoxia in healthy humans. Despite chronically increased sympathetic activity, the vasodilation induced by acute hypoxia appears to be largely preserved in patients with sleep apnea. Collectively, these findings support the central hypothesis that intermittent hypoxia alters sympathetic activity and reflex function, and evokes compensatory peripheral vascular adaptations, possibly via oxidative stress.
The specific aims of this proposal are to determine whether: (1) experimental intermittent hypoxia alters sympathetic reflex function, and whether this effect can be prevented by ascorbic acid;(2) skeletal muscle vascular adaptations to hypoxic stress are in part dependent on enhanced endothelium-derived hyperpolarizing factor, and is characteristic of nitric oxide deficient states due to enhanced oxidative stress;(3) cigarette smoking is associated with altered neurocirculatory control due to enhanced oxidative stress and is restored in part with ascorbic acid;and (4) reflex vasoconstrictor mechanisms are altered in peripheral arterial disease and act to restrict collateral blood flow in the ischemic limb. The proposed studies expand the scope of our prior work on neurocirculatory regulation during hypoxia and will provide new insight into the mechanisms that link intermittent hypoxia to adverse cardiovascular outcomes.
This research examines mechanisms that control peripheral blood fiow after intermittent or chronic exposure to physiological stress. These mechanisms appear to be disturbed in important ways in highly common. condifions such as obstrucfive sleep apnea, peripheral arterial disease, and in smokers. New insight into these processes will help us better understand how these mechanisms contribute to disease progression and will allow us to design better therapies and preventive measures.
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|Luck, J Carter; Miller, Amanda J; Aziz, Faisal et al. (2017) Blood pressure and calf muscle oxygen extraction during plantar flexion exercise in peripheral artery disease. J Appl Physiol (1985) 123:2-10|
|Drew, Rachel C; Blaha, Cheryl A; Herr, Michael D et al. (2017) Muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction in healthy humans. Am J Physiol Regul Integr Comp Physiol 312:R956-R964|
|Xing, Jihong; Li, Jianhua (2017) Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion. Cell Physiol Biochem 44:163-171|
|Drew, Rachel C (2017) Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology. Am J Physiol Regul Integr Comp Physiol 313:R654-R659|
|Cui, Jian; Boehmer, John; Blaha, Cheryl et al. (2017) Muscle sympathetic nerve activity response to heat stress is attenuated in chronic heart failure patients. Am J Physiol Regul Integr Comp Physiol 312:R873-R882|
|Xing, Jihong; Li, Jianhua (2017) TRPA1 Function in Skeletal Muscle Sensory Neurons Following Femoral Artery Occlusion. Cell Physiol Biochem 42:2307-2317|
|Ross, Amanda J; Gao, Zhaohui; Luck, Jonathan Carter et al. (2017) Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease. Ann Vasc Surg 38:260-267|
|Xing, Jihong; Li, Jianhua (2016) The Role Played by Adenosine in Modulating Reflex Sympathetic and Pressor Responses Evoked by Stimulation of TRPV1 in Muscle Afferents. Cell Physiol Biochem 40:39-48|
|Muller, Matthew D; Li, Zhijun; Sica, Christopher T et al. (2016) Muscle oxygenation during dynamic plantar flexion exercise: combining BOLD MRI with traditional physiological measurements. Physiol Rep 4:|
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